Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
Link to SEPIO compliant JSON-LD document
  • There was no gene found in the curated document received from the VCI/VCEP
  • Gene listed was thus derived from ClinVar and/or CAR
  • The variant label for this record ("NC_012920.1(MT-CYB"):m.15467A>G) does not appear to be in HGVS format

Variant: NC_012920.1(MT-CYB):m.15467A>G

CA913173949

618216 (ClinVar)

Gene: MT-CYB
Condition: mitochondrial disease
Inheritance Mode: Mitochondrial inheritance
Link to MONDO
UUID: ea02787f-fdf0-4f54-9e45-3f7b1e9a3e57

HGVS expressions

NC_012920.1:m.15467A>G
J01415.2:m.15467A>G
ENST00000361789.2:n.721A>G

Uncertain Significance

Met criteria codes 1
BP4
Not Met criteria codes 10
PS3 PS2 PS4 PP3 PP1 PM2 PM6 BA1 BS3 BS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Mitochondrial Disease Nuclear and Mitochondrial Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1_mtDNA

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Mitochondrial Diseases VCEP
The m.15467A>G (p.T241A) variant in MT-CYB was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel on March 28, 2023. There are no individuals or families with this variant reported in the medical literature to our knowledge. There are several occurrences in population databases. This variant is present in 0.083% of individuals in GenBank MITOMAP sequences (49/59,389; including multiple individuals from haplogroup T1a), in 0.023% of individuals in gnomAD v3.1.2 (13/56,431; 13 homoplasmic occurrences, seen in individuals from several haplogroups), and in 0.031% of individuals in the Helix dataset (60/195,983; seen in individuals from several haplogroups). In silico tools (APOGEE) predict this variant to be neutral (score of 0.47, BP4). There are no cybrid, single fiber, or other studies reported for this variant. In summary, this variant meets criteria to be classified as uncertain significance for primary mitochondrial disease inherited in a mitochondrial manner. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Variant Curation Expert Panel on March 28, 2023. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): BP4.
Met criteria codes
BP4
In silico tools (APOGEE) predict this variant to be neutral (score of 0.47, BP4).
Not Met criteria codes
PS3
There are no cybrid, single fiber, or other studies reported for this variant.
PS2
There are no individuals or families with this variant reported in the medical literature to our knowledge.
PS4
There are no individuals or families with this variant reported in the medical literature to our knowledge.
PP3
In silico tools (APOGEE) predict this variant to be neutral (score of 0.47, BP4).
PP1
There are no individuals or families with this variant reported in the medical literature to our knowledge.
PM2
There are several occurrences in population databases. This variant is present in 0.083% of individuals in GenBank MITOMAP sequences (49/59,389; including multiple individuals from haplogroup T1a), in 0.023% of individuals in gnomAD v3.1.2 (13/56,431; 13 homoplasmic occurrences, seen in individuals from several haplogroups), and in 0.031% of individuals in the Helix dataset (60/195,983; seen in individuals from several haplogroups).
PM6
There are no individuals or families with this variant reported in the medical literature to our knowledge.
BA1
There are several occurrences in population databases. This variant is present in 0.083% of individuals in GenBank MITOMAP sequences (49/59,389; including multiple individuals from haplogroup T1a), in 0.023% of individuals in gnomAD v3.1.2 (13/56,431; 13 homoplasmic occurrences, seen in individuals from several haplogroups), and in 0.031% of individuals in the Helix dataset (60/195,983; seen in individuals from several haplogroups).
BS3
There are no cybrid, single fiber, or other studies reported for this variant.
BS1
There are several occurrences in population databases. This variant is present in 0.083% of individuals in GenBank MITOMAP sequences (49/59,389; including multiple individuals from haplogroup T1a), in 0.023% of individuals in gnomAD v3.1.2 (13/56,431; 13 homoplasmic occurrences, seen in individuals from several haplogroups), and in 0.031% of individuals in the Helix dataset (60/195,983; seen in individuals from several haplogroups).
Approved on: 2023-03-28
Published on: 2023-03-29
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